Asthma is a chronic inflammatory disorder of the airway. Multiple lines of evidence suggest that Th2 inflammation is a cornerstone of asthma pathogenesis. Th2 inflammation is also an essential component of host anti-parasite and anti-fungal immunity. In fact, the Th2 inflammatory response in the asthmatic airway has been proposed to be a parasite-independent anti-parasite inflammatory reaction. Chitin, the second most abundant glycopolymer in biology, is an integral component of the walls of parasites, crustaceans, and fungi where it protects them from potentially deleterious aspects of their environment. Chitin containing organisms also produce chitinases to allow them to molt and grow. Without these chitinases their lifecycle is aborted and death ensues. As a result, chitinase production is an essential part of the immune response to parasites and infectious agents in a large number of lower life forms. In addition, chitinase inhibitors have been developed to control infections with chitin-containing organisms. Interestingly, chitin and chitin synthase do not exist in man. However, human chitinase genes have recently been discovered and human chitinases have been shown to be potently induced at sites of Th2 inflammation. Virtually nothing is known, however, about the role(s) that chitinases play in mammalian or human physiology. In keeping with the intimate relationship between anti-parasite and allergic Th2 inflammatory responses, we speculated that elements that are critical in anti-parasite Th2 inflammation also play an essential role in allergic/asthmatic Th2 responses. To test this concept we studied the role of acidic mammalian chitinase (AMCase), a 50 kD protein product, in allergic inflammation. Our studies demonstrate that AMCase is prominently induced in macrophages and epithelial cells at sites of Th2 inflammation. They also demonstrate that AMCase has prominent chitinase activity and that blocking AMCase production and or biological activity markedly ameliorates aeroallergen-induced Th2 inflammation. They also suggest that this protective effect is due to the ability of AMCase inhibition to selectively inhibit IL-13 effector pathways since AMCase inhibition also ameliorated the phenotypes induced by IL-13 in constitutive and inducible lung-targeted overexpression transgenic murine asthma models.